POS0109 CAN GAIT PATTERNS IN KNEE OSTEOARTHRITIS PATIENTS BE EXPLAINED OR PREDICTED BY JOINT STRUCTURE?
Authors: M. Jansen, D. Hodgins, S. Mastbergen, M. Kloppenburg, F. J. Blanco, I. K. Haugen, F. Berenbaum, F. Lafeber, F. Roemer, W. Wirth
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> This study uses gait measurements and imaging techniques in knee osteoarthritis (OA) patients to investigate the association between gait patterns and joint structure. <h3>Objectives</h3> To analyze whether 1) gait patterns can be explained by joint structure and 2) longitudinal gait alterations can be predicted by joint structure in people with knee OA. <h3>Methods</h3> In the IMI-APPROACH cohort, 297 people with knee OA were included at 5 sites in Europe. At baseline and two years, full gait kinematic data was collected from all participants using the GaitSmart system (Dynamic Metrics Limited, Codicote, UK). Radiographs and MRI scans of their index knee were performed for evaluation of joint structure. The GaitSmart measures included for the current study were range of motion (ROM) of the hip, thigh, knee in swing and stance phase, and calves in the sagittal plane, and medial-lateral movement of the thigh and calf, all for the index leg. Stride duration and speed were included as well. From the radiographs, the minimum joint space width (JSW), femorotibial angle, mean whole-joint subchondral bone density (SBD), and total whole-joint osteophyte area were determined. From the MRI scans, mean whole-joint femorotibial cartilage thickness (FTC) was determined and MOAKS scoring for synovitis, effusion, meniscus signal and meniscal extrusion were performed. For the meniscal parameters, the maximum score across all regions was used. All GaitSmart parameters were compared between baseline and two years with paired t-tests to quantify gait alterations over two years. For the comparisons with joint structure, principal component analyses (PCA) was performed on the gait parameters first, to discover underlying domains. Univariate backwards linear regression models with each of the GaitSmart domains as dependent variable were used to analyze how joint structure influences gait or predicts gait change over two years. Three models were run: one with participant demographics (age, sex, BMI) only, one with structural imaging parameters only, and one combining the first two models. <h3>Results</h3> 284 Participants (age 66.5±7.1, BMI 28.0±5.4, 65 (23%) male, 154 (54%) radiographic OA) had baseline GaitSmart data (211 had two-year data). PCA identified three gait domains: upper leg (speed, duration, thigh ROM and hip ROM), lower leg (knee ROM in stance and swing, calf ROM), and medial-lateral movement (thigh and calf medial-lateral movement). Over two years the lower leg parameters showed a slight deterioration, though only knee ROM in swing phase changed significantly (-1.5±6.9 degree, p=0.002). The upper leg parameters showed minor non-significant improvement over two years; the medial-lateral parameters showed opposing non-significant changes. Results of all models are summarized in Table 1. Cross-sectionally, male sex, higher BMI, higher SBD and synovitis absence were associated with worse upper leg function. Change in upper leg gait was predicted by sex only, with male sex resulting in less function improvement. For lower leg gait, female sex, higher BMI, bigger osteophytes, higher FTC, absence of effusion and presence of synovitis lead to worse function (i.e. larger ROM) cross-sectionally. Worsening lower leg gait could be predicted by higher age and BMI, presence of synovitis and smaller osteophytes. Neither demographics nor joint structure was significantly associated with or predictive for changes in medial-lateral gait. <h3>Conclusion</h3> Joint structure could partially explain gait and even predict gait changes in people with knee OA especially for the lower leg, providing a significant association between OA symptoms and joint structure, although only for a limited part (low R<sup>2</sup> values; Table 1) and not for medial-lateral movement. Surprisingly, synovitis and osteophyte size showed contrasting associations with lower leg gait that may be explained by half of the patients not having radiographic OA and should be investigated further. Parameters indicating more severe OA (e.g. lower JSW and FTC, higher age and SBD) were generally associated with more impaired gait. <h3>Acknowledgements</h3> This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (APPROACH grant n° 115770). This communication reflects the views of the authors and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein. See www.imi.europe.eu and www.approachproject.eu. <h3>Disclosure of Interests</h3> Mylène Jansen: None declared, Diana Hodgins Employee of: Founder and technical director of GaitSmart, Simon Mastbergen: None declared, Margreet Kloppenburg Consultant of: Fee for consultancy/advisory boards by Abbvie, Pfizer, Kiniksa, Flexion, Galapagos, Jansen, CHDR, Novartis, UCB, Francisco J. Blanco Grant/research support from: Gedeon Richter Plc., Bristol-Myers Squibb International corporation (BMSIC), Sun Pharma Global FZE, Celgene Corporation, Janssen Cilag International N.V, Janssen Research &amp; Development, Viela Bio, Inc., Astrazeneca AB, UCB BIOSCIENCES GMBH, UCB BIOPHARMA SPRL, AbbVie Deutschland GmbH &amp; Co.KG, Merck KGaA, Amgen, Inc., Novartis Farmacéutica, S.A., Boehringer Ingelheim España, S.A, CSL Behring, LLC, Glaxosmithkline Research &amp; Development Limited, Pfizer Inc, Lilly S.A., Corbus Pharmaceuticals Inc., Biohope Scientific Solutions for Human Health S.L., Centrexion Therapeutics Corp., Sanofi, MEIJI FARMA S.A., Kiniksa Pharmaceuticals, Ltd, Fundación para la Investigación Biomédica Del Hospital Clínico San Carlos, Ida K. Haugen Speakers bureau: Novartis, GSK, Grant/research support from: Pfizer/Lily, Francis Berenbaum Shareholder of: 4Moving Biotech, Peptinov and 4Pharm, Speakers bureau: Expanscience, Pfizer, Viatris, Paid instructor for: Expert testimony Pfizer and Eli Lilly, Consultant of: AstraZeneca, Boehringer Ingelheim, Bone Therapeutics, Cellprothera, Galapagos, Gilead, Grunenthal, GSK, Eli Lilly, MerckSerono, MSD, Nordic Bioscience, Novartis, Pfizer, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, 4P Pharma, Grant/research support from: TRB Chemedica and Pfizer, Employee of: CEO-CMO of 4Moving Biotech, Floris Lafeber: None declared, Frank Roemer Shareholder of: Boston Imaging Core Lab (BICL), LLC, Consultant of: Calibr and Grünenthal GmbH, Wolfgang Wirth Shareholder of: Chondrometrics GmbH, Employee of: Chondrometrics GmbH.